Hepatic Cell News Volume 1.20 | Jun 16 2017

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Bioengineered Livers Mimic Natural Development

Investigators used novel genomic and stem cell technologies to understand how individual cells work together and use their genomes to develop into human liver tissue. This new research advances efforts to bioengineer healthy and usable human liver tissue from human pluripotent stem cells. [Press release from the Max Planck Institute discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Sulforaphane Reduces Hepatic Glucose Production and Improves Glucose Control in Patients with Type 2 Diabetes

Scientists analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, they identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2–related factor 2 and decreased expression of key enzymes in gluconeogenesis. [Sci Transl Med] Full Article | Press Release

Calcium Binding Protein 39 Promotes Hepatocellular Carcinoma Growth and Metastasis by Activating ERK Signaling Pathway

Researchers report that the calcium binding protein (CAB39) was frequently up-regulated in hepatocellular carcinoma, which was significantly associated with tumor metastasis, poorer disease-free survival rate and poor prognosis. They found that CAB39 contributed to the ERK pathway activation and mutations of the key sites of CAB39 markedly decreased the level of the phosphorylated ERK. [Hepatology] Abstract

Exosomes Derived from Palmitic Acid-Treated Hepatocytes Induce Fibrotic Activation of Hepatic Stellate Cells

The authors investigated the role of exosomes in non-alcoholic fatty liver disease progression. A microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and palmitic acid (PA)-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. [Sci Rep] Full Article

SerpinB3 Promotes Pro-Fibrogenic Responses in Activated Hepatic Stellate Cells

Investigators analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis. In vitro experiments revealed that SerpinB3 addition to either primary cultures of human activated myofibroblast-like hepatic stellate cells or human stellate cell line strongly up-regulated the expression of genes involved in fibrogenesis and promoted oriented migration, but not cell proliferation. [Sci Rep] Full Article

TIP30 Regulates Lipid Metabolism in Hepatocellular Carcinoma by Regulating SREBP1 through the Akt/mTOR Signaling Pathway

Researchers examined the effects of tumor suppressor TIP30 on the regulation of hepatocellular carcinoma (HCC) lipid metabolism. They found that decreased TIP30 expression leads to elevated fatty acid synthesis and enhanced levels of lipogenic enzymes SCD and FASN in HCC cells. [Oncogenesis] Full Article

Lysosome-Mediated Degradation of a Distinct Pool of Lipid Droplets during Hepatic Stellate Cell Activation

Scientists investigated the mechanisms of neutral lipid metabolism in the pre-existing lipid droplet (LD) pool. To investigate the involvement of lysosomal degradation of neutral lipids, they studied the effect of lalistat, a specific lysosomal acid lipase (LAL) inhibitor on LD degradation in hepatic stellate cells (HSCs) during activation in vitro. The LAL-inhibitor increased the levels of TAG, CE and RE in both rat and mouse HSCs. [J Biol Chem] Abstract | Full Article

Hepatoprotective Effect of Aqueous Extract from the Seeds of Orychophragmus violaceus against Liver Injury in Mice and HepG2 Cells

Researchers investigated the effect of O. violaceus seeds on liver injury and further explored the molecular mechanism of the beneficial effects using aqueous extract from the seeds of O. violaceus (AEOV). They found that AEOV attenuated liver injury induced by CCl₄ as evidenced by decreased levels of alanine aminotransferase and aminotransferase in serum, improvement of liver histopathological changes, and substantial attenuation of oxidative stress and inflammation via regulation of nuclear factor-erythroid 2-related factor-2 and nuclear factor κB pathways. [Int J Mol Sci] Full Article

Autocrine Human Growth Hormone Promotes Invasive and Cancer Stem Cell-Like Behavior of Hepatocellular Carcinoma Cells by STAT3 Dependent Inhibition of CLAUDIN-1 Expression

The authors investigated the mechanism of the oncogenic effects of human growth hormone (hGH) in hepatocellular carcinoma (HCC) cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported. [Int J Mol Sci] Full Article

MicroRNA-4458 Suppresses the Proliferation of Human Lung Cancer Cells In Vitro by Directly Targeting Lin28B

Scientists investigated the direct target of miR-4458 and its biological functions in human lung cancer cells. In dual-luciferase reporter assay, they found that miR-4458 mimicked dose-dependently and inhibited the luciferase activity of the wild-type 3′UTR of Lin28B in human lung cancer A549 and NCI-H1299 cell lines without affecting its mutant forms. [Acta Pharmacol Sin] Abstract

Hepatokines: Linking Nonalcoholic Fatty Liver Disease and Insulin Resistance

The authors describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication. [Nat Rev Endocrinol] Abstract

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IBBR Awarded $6 Million NIH Grant for Structure-Based Design of a Hepatitis C Vaccine

University of Maryland’s Institute for Bioscience and Biotechnology Research (IBBR) has been awarded a $6.0 million grant entitled, “Structure-Based Vaccine Design for Hepatitis C Virus”, to develop a novel prophylactic vaccine to prevent hepatitis C virus infection. [University of Maryland’s Institute for Bioscience and Biotechnology Research] Press Release

Sirnaomics Advances Leading siRNA Therapeutic Candidate, STP705, for Treatment of Liver Fibrosis

Sirnaomics, Inc. announced that it has received reports from efficacy studies with CCL4-Induced mouse liver fibrosis model for its lead siRNA therapeutic candidate, STP705, from two contract research companies. [Sirnaomics, Inc.] Press Release

Q BioMed Inc. Finalizes License Agreement with Oklahoma Medical Research Foundation and the Rajiv Gandhi Centre for Biotechnology for Novel Liver Cancer Treatment

Q BioMed Inc. announced entry into a final license agreement with The Oklahoma Medical Research Foundation and the Rajiv Gandhi Centre for Biotechnology. Under the agreement QBioMed has the global exclusive rights to develop and market a novel chemotherapeutic drug to treat liver cancer. [Q BioMed Inc.] Press Release

Biologists Debate How to License Preprints

Biology’s zeal for preprints — papers posted online before peer review — is opening up a thorny legal debate: should scientists license their manuscripts on open-access terms? Researchers have now shared more than 11,000 papers at the popular bioRxiv preprints site. But where some researchers allow their bioRxiv manuscripts to be freely redistributed and reused, others have chosen to lock them down with restrictive terms. [Nature News] Editorial

Indian Research Labs Face Financial Crisis

India’s 38 premier scientific laboratories are in a budgetary pinch. A jump in expenditures on salaries, pensions, and perks for government employees, recommended by an advisory commission, is leaving little money for new research in the budget of the Council of Scientific & Industrial Research, based in New Delhi, which oversees the labs and their 4600 scientists. [ScienceInsider] Editorial

Texas Has Sanctioned Unapproved Stem Cell Therapies. Will It Change Anything?

Texas Governor Greg Abbott signed a bill allowing clinics and companies in the state to offer people unproven stem cell interventions without the testing and approval required under federal law. Like the “right to try” laws that have sprung up in more than 30 states, the measure is meant to give desperately ill patients access to experimental treatments without oversight from the U.S. Food and Drug Administration. [ScienceInsider] Editorial

Empty Rhetoric over Data Sharing Slows Science

Government agencies lack the funds to build platforms for data sharing and resist taking responsibility for such infrastructure. They may hope that universities will host data, but the development of institutional repositories is patchy, and to rely on them is effectively to discourage common data standards and curation. [Nature News] Editorial

NEW Tumor Immunology and Immunotherapy
October 1-4, 2017
Boston, Massachusetts, United States

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NEW PhD Studentship – Hepatic Disease Research (Sanofi)

NEW PhD Studentship Positions – Cell-Free Synthesis of Membrane Proteins (Fraunhofer IZI-BB)

Postdoctoral Associate – Gene Therapy (University of Massachusetts Medical School)

Research Fellow – Cancer Research (National University of Singapore)

Postdoctoral Position – Novel Molecular and Cellular Mechanisms of Liver and Pancreatic Carcinogenesis (University of Illinois College of Medicine)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Fellow – Obesity-Associated Complications (University of Kentucky College of Medicine)

Postdoctoral Position – Pediatrics/Cell Biology (Washington University School of Medicine)

Scientist – Hepatic Nuclear Receptor Biology (Moderna Therapeutics)

Research Technician II – Translational Liver Cancer (Fred Hutchinson Cancer Research Center)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

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